Seven cyclic nucleotide phosphodiesterase (PDE) gene families (Types I- VII) have been identified. We have cloned and expressed representatives of two sub-types of Type III cGMP-inhibited (cGI) PDEs, rat (R) and Human (H) cGIP1 and 2. A membrane-associated adipocyte cGI PDE (McGIP1 isoform) appears during differentiation of 3T3-L1 adipocytes. To learn more about the regulation of McGIP1 gene expression we cloned the cDNA for the cGI-PDE from a mouse adipocyte lambda gt 11 cDNA library (McGIP1 cDNA) The open reading frame of 3303 nucleotides is very similar to the sequence of RcGIP1 cDNA; the carboxyl-terminal region includes the putative catalytic domain highly conserved among mammalian PDEs. On Northern blots, McGIP1 cDNA hybridizes with a prominent approx. 5.5-kb band in poly(A)+ RNA from mouse adipose tissue, testis, liver, lung, and cerebellum, but not heart. Active recombinant McGIP1 was expressed in Sf9 cells transfected with recombinant baculovirus vector.